The heart is the center of a person's circulatory system. It includes an electro-mechanical system performing two major pumping functions. The heart includes four chambers: right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV). The left portions of the heart, including LA and LV, draw oxygenated blood from the lungs and pump it to the organs of the body to provide the organs with their metabolic needs for oxygen. The right portions of the heart, including RA and RV, draw deoxygenated blood from the body organs and pump it to the lungs where the blood gets oxygenated. The heart performs these mechanical pumping functions cyclically. Each cycle, known as the cardiac cycle, includes systole and diastole. Systole is the ejection phase of the cardiac cycle, during which the ventricles eject blood. Diastole is the relaxation phase of the cardiac cycle. Primary functions of diastole include filling the ventricles with blood for the next ejection (systolic) phase and allowing perfusion of the myocardial tissue. The filling of the LV includes a fast (active) filling phase followed by a slow (passive) filling phase. During the fast filling phase, the walls of LV spring back to their relaxation state after blood ejection, thereby drawing blood from the LA into the LV. During the slow filling phase, blood continues to be drawn into the LV by a pressure gradient between the LA and the LV.
In a normal heart, the sinus node, the heart's natural pacemaker, generates electrical signals, called action potentials, that propagate through an electrical conduction system to various regions of the heart to excite the myocardial tissues of these regions. Coordinated delays in the propagations of the action potentials in a normal electrical conduction system cause the various portions of the heart to contract in synchrony to result in efficient pumping functions. A blocked or otherwise abnormal electrical conduction and/or deteriorated myocardial tissue cause dysynchronous contraction and relaxation of the heart, resulting in poor hemodynamic performance, including a diminished blood supply to the heart and the rest of the body. The abnormal electrical conduction and/or deteriorated myocardium result in systolic dysfunction—because the myocytes do not contract in unison—and diastolic dysfunction—because the myocytes do not relax in unison. The relative degree of diastolic and systolic impairment will vary during different stages of the disease. Decreased systolic and diastolic performance each contribute to overall hemodynamic performance.
For these and other reasons, there is a need for providing an effective treatment for the diastolic dysfunction.